DAPT with Clopidogrel and Aspirin Benefits Mild Ischemic Stroke Patients When Started Within 72 Hours: INSPIRES Trial

In the research conducted in China, these patients benefited significantly from starting dual antiplatelet therapy (DAPT) with clopidogrel and aspirin, compared to treatment with aspirin alone. This benefit was consistent when the dual therapy was initiated within 72 hours of symptom onset.

The trial also noted a similar increase in the risk of moderate-to-severe bleeding with both treatment approaches. Consequently, it is recommended that patients receive DAPT with clopidogrel and aspirin within 72 hours of symptom onset to optimize treatment outcomes.

Previous studies have demonstrated that DAPT can lower the risk of early recurrent stroke in patients with acute mild ischemic stroke or TIA when administered within 24 hours of symptom onset. However, it remains unclear whether initiating dual antiplatelet therapy beyond this 24-hour window can still effectively reduce the risk of early recurrent stroke. Therefore, Yuetong Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and colleagues aimed to evaluate the safety and efficacy of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours from more than 24 hours to 48 hours, and more than 48 hours to 72 hours.

The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial study conducted across 222 hospitals in China. The trial included patients with acute mild ischemic stroke and TIA and divided them into three groups based on the time from symptom onset to randomization: group 1 (≤24 hours), group 2 (>24 to ≤48 hours), and group 3 (>48 to 72 hours). Patients were monitored for 90 days.

Participants received either clopidogrel combined with aspirin or aspirin alone. For the dual therapy, the regimen consisted of a 300 mg loading dose of clopidogrel on the first day, followed by 75 mg daily from days 2 to 90, and aspirin administered at 100 to 300 mg on the first day, then 100 mg daily from days 2 to 90. Alternatively, patients receiving aspirin alone took 100 to 300 mg on the first day and 100 mg daily from days 2 to 90. All treatments were started within 72 hours of symptom onset.

The primary outcome of the study was the incidence of new stroke, whether ischemic or hemorrhagic, within the 90-day follow-up period. The main safety outcome was the occurrence of moderate-to-severe bleeding, assessed using the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria.

The study led to the following findings:

• The analysis included 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65, and 64.2% of patients were male.
• In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 12.4% of patients; among those randomized from more than 24 hours to 48 hours, 8.3% among those randomized from more than 24 hours to 48 hours, and in 7.0% patients.
• The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% versus 8.2%; hazard ratio [HR], 0.70), of more than 24 to 48 hours (7.6% versus 8.9%; HR, 0.85), and of 24 hours or less (11.5% versus 13.4%; HR, 0.83).
• Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 0.9% of patients in the clopidogrel-aspirin group and 0.4% in the aspirin-alone group (HR, 2.00), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 0.7% patients in the clopidogrel-aspirin group and 0.3% patients in the aspirin-alone group (HR, 2.25) and in those with time to randomization of within 24 hours, occurred in 1.5% patients in the clopidogrel-aspirin group and 0.8% patients in the aspirin-alone group (HR, 1.57).

"The study results indicate that initiating DAPT with clopidogrel and aspirin within 72 hours of symptom onset can be beneficial for patients with mild ischemic stroke or TIA, without significantly increasing the risk of moderate-to-severe bleeding," the researchers concluded.

Reference:

Liu Y, Zhao J, Gao Y, et al. Clopidogrel and Aspirin Initiated Between 24 to 72 Hours for Mild Ischemic Stroke: A Subgroup Analysis of the INSPIRES Randomized Clinical Trial. JAMA Netw Open. 2024;7(9):e2431938. doi:10.1001/jamanetworkopen.2024.31938